Thursday, September 6, 2018

How to interpret the literature: A new series of posts

The Salty Statistician will be a recurring feature of this blog wherein we ask statisticians in medicine to break down articles from the surgery literature and assess whether the reported conclusions are supported by the data. Let’s look at this study:

Groh MA et al. Is Surgical Intervention the Optimal Therapy for the Treatment of Aortic Valve Stenosis for Patients With Intermediate Society of Thoracic Surgeons Risk Score? Annals of Thoracic Surgery.

The authors attempted to address the question of whether aortic stenosis patients deemed “intermediate risk” [IR] for surgical aortic valve replacement [AVR] are best treated with open surgery or transcatheter AVR. The authors looked at 1,144 patients who received surgical AVR from 2008-2014 at a single center focusing on the 620 “intermediate risk” patients. At the end of the follow-up period, 72 had died.

Unfortunately, major methodological issues undermine the paper’s conclusions. Fortunately, this provides an excellent teaching opportunity.

First, the authors inappropriately used logistic regression to analyze independent predictors of mortality. Logistic regression treats the outcome as a simple “Yes” or “No” variable, while ignoring the time-at-risk. This study included patients treated over a six-year period (2008-2014) who therefore have substantial differences in the amount of time at risk. Consider the following hypothetical patients.

Patient A treated in 2008 and died in 2014 surviving six years after surgery. The logistic regression model simply counts patient A as “dead.”

Patient B treated in 2014 and alive in 2017 but dies in 2018, after the data were analyzed and the paper published. He survived four years after surgery and in the logistic regression model, counts as “alive” since data were analyzed in 2017.

Patient A lived for six years after surgery, but counts as “worse” in the analysis than Patient B who only lived for four years because of the time at which the data were “frozen” and analyzed. Of course, this is unavoidable in long-term outcomes studies, but one must choose an appropriate statistical method that accounts for time-at-risk.

Cox proportional-hazards models are more appropriate for a long-term survival outcome than logistic regression. When building a Cox model, one specifies both the current status (i.e., alive/dead) as well as an amount of follow-up time. For example, Patient A is “dead” with six years of follow-up; Patient B is “alive” but with only three years of follow-up. This provides a proper assessment of how strongly the independent variables are associated with risk of mortality while accounting for the unequal follow-up time.

Second, the authors state their data supports the conclusion that “SAVR is the optimal therapy for most of the patients” in the IR group in comparison to TAVR. However, their paper lacks any data on outcomes in IR patients who were treated with TAVR. Why the authors believe presenting data from a series of SAVR patients is sufficient to claim that SAVR is the “optimal therapy” absent any comparison data on patients treated with TAVR is unclear. Randomized controlled trials have more appropriately compared SAVR and TAVR in the IR population. Link here and here.

Which patients should receive surgical AVR versus transcatheter AVR is a good question, but to answer it, the paper used an incorrect approach.

Final Rating (1-5 Scalpels): 1 Scalpel - significant methodological issues

This issue of the Salty Statistician was written by Andrew Althouse (@ADAlthousePhD), currently an Assistant Professor of Medicine at the University of Pittsburgh as well as Statistical Editor of Circulation: Cardiovascular Interventions.

We intend this series to focus on work that is perceived to have a high impact on clinical practice, so we welcome reader suggestions. If you have a paper that you would like to see reviewed as part of the Salty Statistician series, please tweet @Skepticscalpel or @ADAlthousePhD or email We cannot promise that all submissions will be reviewed in this space, but we will do our best.


Oldfoolrn said...

If you really want to peruse studies that make your head spin, try "nursing research." If nurses really want to contribute helpful data they should be doing clinical research to benefit patients not some mumbo jumbo filled studies with psychobabble designed to muddy the issue. Nursing research was created by nurse office sitters to differentiate diploma school nursing education from baccalaureate academic education-nothing wrong with that if it provided useful information but we wind up with things like the bouffant vs cap fight or awards for unproven Bovie smoke mitigation devices.

Skeptical Scalpel said...

Thanks for your comment. I couldn’t agree more.

frankbill said...

Here is a something that should be discussed my all medical providers but will be surprised if there is much interest in any one wanting to discuss it.

In part Clinical Practice Guideline for Management of Primary Aldosteronism: What is New in the 2016 Update?
Damian G Romero1,2,3,* and Licy L Yanes Cardozo2,3,4,5,*
Author information ► Copyright and License information ► Disclaimer

Go to:
Primary Aldosteronism is the single most common cause of secondary hypertension and is associated with increased target organ injury. The Endocrine Society has recently released the updated Clinical Practice Guideline for Primary Aldosteronism entitled “The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline”. We review the updated Clinical Practice Guideline, highlighting the new recommendations and the implications that they may have in clinical practice. The recognition by the Endocrine Society’s Task Force that Primary Aldosteronism is a public health issue and that the population at risk for screening should be significantly expanded will surely have an impact in the clinical practice which hopefully will translate in better detection, diagnosis and treatment of patients with Primary Aldosteronism.

How common is Primary Aldosteronism?
Multiple epidemiological studies in the last two decades have shown that PA has a prevalence of >5% (possible even >10%) of hypertensive patients, both in general and specialty settings.

frankbill said...

I know this isn't quite what this posting is about. But maybe it needs to be discussed.

In the past when Skeptical Scalpel posts about research publications seens not many respond to the post. I often wounder if providers don't care about ongoing research and don't beleve it will help them provide better care for there patients.

Case in point is all the new research about Primary Aldosteronism. In the past Providers were lead to beleave that it was very rare and they would likely not see many with Primary Aldosteronism.

About all the research done Primary Aldosteronism in the past ten years state 5% or more that have hypertension is due to Primary Aldosteronism. It would seem if this true then most providers have seen many with Primary Aldosteronism. Yet I have asked many providers about this and am still being told it is very rare any one would have it.

As my above posting states Primary Aldosteronism is the single most common cause of secondary hypertension and is associated with increased target organ injury. It is also very treatable and many times is cured by surgay. So why are providers still not up to date on this?

Skeptical Scalpel said...

Frank, thanks for commenting. I know primary aldosteronism is near and dear to your heart. I think the reason that nobody is commenting on your posts is that mine is a primarily surgical audience. I doubt many people who read my blog have cared for even one case of aldosteronism. They don't feel the need to be up to date on the topic.

frankbill said...

Since surgery is recommended for most with primary aldosteronism then would think some surgeons need to be up to date.

I would guess that some surgeons have hypertension and at least 5% of them have primary aldosteronism. Does this 5% not care if they are subject to increased target organ injury?

Skeptical Scalpel said...

I don't know if any endocrine surgeons follow my blog. Even if they do so, they may already be aware of a guideline that came out in 2016. I know it's surprising to many people, but surgeons usually keep current on topics like this--particularly if they perform adrenalectomies.

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